Methods and Apparatus for Decomposing Tandem Mass Spectra Generated by All-Ions Fragmentation

Abstract

A method for tandem mass spectrometry of a plurality of eluting compounds comprises: (a) performing, during a time period, the steps of: ionizing the plurality of eluting compounds to generate a plurality of precursor ion species; introducing the plurality of precursor ions into a fragmentation cell operated at constant fragmentation energy so as to generate a plurality of product-ion species from at least a portion of the precursor ion species; and generating a mass spectrum of the plurality of product-ion species; and (b) recognizing matches between certain of the product ion species generated during the time period based on correlations between elution profiles of the product ion species.

What is claimed is: 
     
         1 . A method for acquiring and interpreting tandem mass spectra of a plurality of compounds that are introduced into a mass spectrometer from a chromatograph, said method comprising:
 (a) repeatedly performing, during a time period, the steps of:
 (a1) ionizing the plurality of compounds as they elute from the chromatograph so as to generate a plurality of precursor ion species therefrom using an ion source of the mass spectrometer; 
 (a2) introducing the plurality of precursor ions into a fragmentation cell of the mass spectrometer operated at constant fragmentation energy so as to generate a plurality of product-ion species from all or a portion of each of the plurality of precursor ion species; and 
 (a3) generating a mass spectrum of the plurality of product-ion species; and 
   (b) recognizing matches between certain of the product ion species generated during the time period based on correlations between elution profiles of the product ion species determined from the plurality of generated mass spectra.   
     
     
         2 . A method as recited in  claim 1 , further comprising identifying at least one of the compounds from a set of matched product ion species. 
     
     
         3 . A method as recited in  claim 1 , further comprising:
 (c) recognizing a mass spectral peak of a residual unfragmented precursor ion species from the plurality of generated mass spectra.   
     
     
         4 . A method as recited in  claim 3 , further comprising:
 (d) determining an elution profile of the residual unfragmented precursor ion species from the plurality of generated mass spectra; and   (e) recognizing a match between the residual unfragmented precursor ion species and at least one product ion species based on at least one correlation between the elution profile of the residual unfragmented precursor ion species and an elution profile of the at least one product ion species.   
     
     
         5 . A method as recited in  claim 3 , further comprising:
 (d) determining a mass of the residual unfragmented precursor ion species; and   (e) recognizing a match between the residual unfragmented precursor ion species and a product ion species based on a correspondence of a mass difference between the residual unfragmented precursor ion species and the product ion species to a loss of a valid neutral molecule.   
     
     
         6 . A method as recited in  claim 3 , further comprising:
 (d) determining a mass of the residual unfragmented precursor ion species; and   (e) recognizing a match between the residual unfragmented precursor ion species and a set of product ion species whose non-adducted masses sum to the non-adducted mass of the individual precursor ion species.   
     
     
         7 . A method as recited in  claim 1 , further comprising:
 (c) receiving, from a user, a mass of a target precursor ion species; and   (d) recognizing a match between the target precursor ion species and a product ion species based on a correspondence of a mass difference between the target precursor ion species and the product ion species to a loss of a valid neutral molecule.   
     
     
         8 . A method as recited in  claim 1 , further comprising:
 (c) receiving, from a user, a mass of a target precursor ion species; and   (d) recognizing a match between the target precursor ion species and a set of product ion species whose non-adducted masses sum to the non-adducted mass of the individual precursor ion species.   
     
     
         9 . A method for acquiring and interpreting tandem mass spectra of a plurality of compounds that are introduced into a mass spectrometer from a chromatograph, said method comprising:
 (a) repeatedly performing a total of m times, during a first time period, the steps of:
 (a1) ionizing the plurality of compounds as they elute from the chromatograph so as to generate a plurality of precursor ion species therefrom using an ion source of the mass spectrometer; 
 (a2) introducing the plurality of precursor ions into a fragmentation or reaction cell of the mass spectrometer so as to generate a plurality of product-ion species from all or a portion of each of the plurality of precursor ion species; and 
 (a3) generating a mass spectrum of the plurality of product-ion species; 
   (b) generating, during the first time period, a total number n of mass spectra of the plurality of precursor ion species prior to their introduction into the fragmentation or reaction cell, wherein n<m; and   (c) recognizing matches between certain of the precursor ion species and certain of the product ion species generated during the first time period based on either correlations between elution profiles of the ion species determined from the plurality of generated mass spectra or correspondences of mass differences between ion species to losses of valid neutral molecules.   
     
     
         10 . A method as recited in  claim 9 , wherein the number n is automatically set so as to be equal to the total number of peaks observed in the elution profiles of the ion species during the first time period. 
     
     
         11 . A method as recited in  claim 9 , wherein the recognized matches are limited to matches between product ions and precursor ions within a list of precursor ions or a list of product ions provided by a user. 
     
     
         12 . A method as recited in  claim 9 , wherein the generation of the mass spectra of the precursor ion species is periodically interleaved with the generation of the mass spectra of the product ion species, during the first time period. 
     
     
         13 . A method as recited in  claim 9 , wherein the recognizing of matches between certain of the precursor ion species and certain of the product ion species further comprises recognizing at least one match between an individual precursor ion species and a set of product ion species whose non-adducted masses sum to the non-adducted mass of the individual precursor ion species. 
     
     
         14 . A method as recited in  claim 9 , wherein the recognizing of matches between certain of the precursor ion species and certain of the product ion species is based on correlations between elution profiles of the ion species if the chromatographic resolution is greater than or equal to a threshold value and is otherwise based on correspondences of mass differences between ion species to losses of valid neutral molecules. 
     
     
         15 . A method as recited in  claim 9 , further comprising:
 (d) repeating steps (a) and (b) during a second time period, wherein a ratio n/m relating to the second time period is different from the ratio n/m relating to the first time period; and   (e) recognizing matches between certain of the precursor ion species and certain of the product ion species generated during the second time period.   
     
     
         16 . A method as recited in  claim 15 , wherein the quantities m and n or the ratio n/m is automatically determined for each of the time periods. 
     
     
         17 . A method as recited in  claim 15 , wherein the recognizing of matches between certain of the precursor ion species and certain of the product ion species generated during the second time period is based on correlations between elution profiles of the ion species or correspondences of mass differences between ion species to losses of valid neutral molecules. 
     
     
         18 . A method for acquiring and interpreting tandem mass spectra of a plurality of compounds that are introduced into a mass spectrometer from a chromatograph, said method comprising:
 (a) repeatedly performing, during a time period, the steps of:
 (a1) ionizing the plurality of compounds as they elute from the chromatograph so as to generate a plurality of precursor ion species therefrom using an ion source of the mass spectrometer; 
 (a2) introducing the plurality of precursor ions into a fragmentation or reaction cell of the mass spectrometer so as to generate a plurality of product-ion species from a portion of each of the plurality of precursor ion species; and 
 (a3) introducing the plurality of product-ion species and a residual portion of the precursor ion species into a mass analyzer of the mass spectrometer so as to generate a mass spectrum thereof; 
   (b) recognizing matches between precursor ion species and product ion species generated during the time period based on either correlations between elution profiles of the ion species determined from the plurality of generated mass spectra or observed correspondences of mass differences between ion species to losses of valid neutral molecules.   
     
     
         19 . A method as recited in  claim 18 , wherein the recognized matches are limited to matches between product ions and precursor ions within a list of precursor ions provided by a user. 
     
     
         20 . A method as recited in  claim 18 , wherein the recognizing of matches between precursor ion species and product ion species further comprises recognizing matches between individual precursor ion species and sets of product ion species whose non-adducted masses sum to the non-adducted mass of the respective individual precursor ion species. 
     
     
         21 . A method as recited in  claim 18 , wherein the recognizing of matches between precursor ion species and product ion species is based on correlations between elution profiles of the ion species if the chromatographic resolution is greater than or equal to a threshold value and otherwise is based on correspondences of mass differences between ion species to losses of valid neutral molecules. 
     
     
         22 . A method as recited in  claim 4 , further comprising identifying at least one of the compounds from a recognized match between a precursor ion species and a product ion species. 
     
     
         23 .- 28 . (canceled)